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Proc Natl Acad Sci U S A
1997 Jul 22;9415:8202-7. doi: 10.1073/pnas.94.15.8202.
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Fixation of allosteric states of the nicotinic acetylcholine receptor by chemical cross-linking.
Watty A
,
Methfessel C
,
Hucho F
.
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Receptor activity can be described in terms of ligand-induced transitions between functional states. The nicotinic acetylcholine receptor (nAChR), a prototypic ligand-gated ion channel, is an "unconventional allosteric protein" which exists in at least three interconvertible conformations, referred to as resting (low agonist affinity, closed channel), activated (open channel), and desensitized (high agonist affinity, closed channel). Here we show that 3,3'-dimethyl suberimidate (DMS) is an agonistic bifunctional cross-linking reagent, which irreversibly "freezes" the nAChR in a high agonist affinity/closed-channel state. The monofunctional homologue methyl acetoimidate, which is also a weak cholinergic agonist, has no such irreversible effect. Glutardialdehyde, a cross-linker that is not a cholinergic effector, fixes the receptor in a low-affinity state in the absence of carbamoylcholine, but, like DMS, in a high-affinity state in its presence. Covalent cross-linking thus allows us to arrest the nAChR in defined conformational states.
Baldwin,
Haemoglobin: the structural changes related to ligand binding and its allosteric mechanism.
1979, Pubmed
Baldwin,
Haemoglobin: the structural changes related to ligand binding and its allosteric mechanism.
1979,
Pubmed
Blount,
Molecular basis of the two nonequivalent ligand binding sites of the muscle nicotinic acetylcholine receptor.
1989,
Pubmed
Campos-Caro,
A single residue in the M2-M3 loop is a major determinant of coupling between binding and gating in neuronal nicotinic receptors.
1996,
Pubmed
,
Xenbase
Changeux,
The acetylcholine receptor: an "allosteric" membrane protein.
,
Pubmed
Czajkowski,
Agonist binding site of Torpedo electric tissue nicotinic acetylcholine receptor. A negatively charged region of the delta subunit within 0.9 nm of the alpha subunit binding site disulfide.
1991,
Pubmed
Davies,
Use of dimethyl suberimidate, a cross-linking reagent, in studying the subunit structure of oligomeric proteins.
1970,
Pubmed
Giraudat,
Structure of the high-affinity binding site for noncompetitive blockers of the acetylcholine receptor: serine-262 of the delta subunit is labeled by [3H]chlorpromazine.
1986,
Pubmed
Giraudat,
Structure of the high-affinity binding site for noncompetitive blockers of the acetylcholine receptor: [3H]chlorpromazine labels homologous residues in the beta and delta chains.
1987,
Pubmed
Heidmann,
Fast kinetic studies on the allosteric interactions between acetylcholine receptor and local anesthetic binding sites.
1979,
Pubmed
Honzatko,
Interactions of phosphate ligands with Escherichia coli aspartate carbamoyltransferase in the crystalline state.
1982,
Pubmed
Hucho,
The ion channel of the nicotinic acetylcholine receptor is formed by the homologous helices M II of the receptor subunits.
1986,
Pubmed
Hucho,
The emerging three-dimensional structure of a receptor. The nicotinic acetylcholine receptor.
1996,
Pubmed
Hucho,
Molecular weight and quaternary structure of the cholinergic receptor protein extracted by detergents from Electrophorus electricus electric tissue.
1973,
Pubmed
Hucho,
The acetylcholine receptor as part of a protein complex in receptor-enriched membrane fragments from Torpedo californica electric tissue.
1978,
Pubmed
Jackson,
Dependence of acetylcholine receptor channel kinetics on agonist concentration in cultured mouse muscle fibres.
1988,
Pubmed
Karlin,
Chemical modification of the active site of the acetylcholine receptor.
1969,
Pubmed
Karlin,
On the application of "a plausible model" of allosteric proteins to the receptor for acetylcholine.
1967,
Pubmed
Karlin,
Toward a structural basis for the function of nicotinic acetylcholine receptors and their cousins.
1995,
Pubmed
KATZ,
A study of the desensitization produced by acetylcholine at the motor end-plate.
1957,
Pubmed
Koshland,
Comparison of experimental binding data and theoretical models in proteins containing subunits.
1966,
Pubmed
Krause,
2.5 A structure of aspartate carbamoyltransferase complexed with the bisubstrate analog N-(phosphonacetyl)-L-aspartate.
1987,
Pubmed
Kurosaki,
Functional properties of nicotinic acetylcholine receptor subunits expressed in various combinations.
1987,
Pubmed
,
Xenbase
Langosch,
Decreased agonist affinity and chloride conductance of mutant glycine receptors associated with human hereditary hyperekplexia.
1994,
Pubmed
,
Xenbase
Lynch,
Identification of intracellular and extracellular domains mediating signal transduction in the inhibitory glycine receptor chloride channel.
1997,
Pubmed
Martin,
The contributions of aspartyl residues in the acetylcholine receptor gamma and delta subunits to the binding of agonists and competitive antagonists.
1996,
Pubmed
Methfessel,
Patch clamp measurements on Xenopus laevis oocytes: currents through endogenous channels and implanted acetylcholine receptor and sodium channels.
1986,
Pubmed
,
Xenbase
MONOD,
ON THE NATURE OF ALLOSTERIC TRANSITIONS: A PLAUSIBLE MODEL.
1965,
Pubmed
Oberthür,
The reaction site of a non-competitive antagonist in the delta-subunit of the nicotinic acetylcholine receptor.
1986,
Pubmed
Pedersen,
d-Tubocurarine binding sites are located at alpha-gamma and alpha-delta subunit interfaces of the nicotinic acetylcholine receptor.
1990,
Pubmed
Perutz,
Mechanisms of cooperativity and allosteric regulation in proteins.
1989,
Pubmed
Schiebler,
Membranes rich in acetylcholine receptor: characterization and reconstitution to excitable membranes from exogenous lipids.
1978,
Pubmed
Schumacher,
Allosteric transition intermediates modelled by crosslinked haemoglobins.
1995,
Pubmed
Sine,
Activation of Torpedo acetylcholine receptors expressed in mouse fibroblasts. Single channel current kinetics reveal distinct agonist binding affinities.
1990,
Pubmed
Unwin,
Arrangement of the acetylcholine receptor subunits in the resting and desensitized states, determined by cryoelectron microscopy of crystallized Torpedo postsynaptic membranes.
1988,
Pubmed
